Cited by 1,655Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 Research

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Long covid—mechanisms, risk factors, and management

Crook, Harry, Raza, Sanara, Nowell, Joseph, Young, Megan, Edison, Paul·2021·BMJ

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Abstract

Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.

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“Long COVID is a multi-system disease affecting heart, lungs, gastrointestinal tract, kidneys, spleen and the liver, as reviewed in detail elsewhere [6, 26, 31].”
Clinical and electrocardiographic correlates of myocardial dysfunction after COVID‐19 in nonhospitalised patients in long‐term follow‐up. Data from the polish long‐covid cardiovascular study
Kapusta, J., Babicki, M., Pieniawska-Śmiech, K., Kałuzińska-Kołat, Ż., Kołat, D., Jankowski, P., Kasprzak, J., Wejner-Mik, P., Bianek-Bodzak, A., & Chudzik, M. (2023) · Journal of Medical Virology · doi:10.1002/jmv.29331 · Cited by 16
“10,11 Choudhury and Mukherjee observed that the SARS ‐ CoV ‐ 2 spike protein can bind to toll ‐ like receptors: TLR1, TLR6 and TLR4 (especially to the latter).”
Background
Omega-3 polyunsaturated fatty acids and the psychiatric post-acute sequelae of COVID-19: A one-year retrospective cohort analysis of 33,908 patients
Liu, T., Ho, C., Chen, D. T.-L., Wu, J., Huang, P., Lai, C., Hsieh, K.-Y., & Su, K. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.09.008 · Cited by 19
“Preliminary guidelines have been emerging for diagnosing and managing long COVID (Crook et al., 2021; Shah et al., 2021; Yelin et al., 2022), and interest is growing in the potential role of anti-inflammatory nutritional or lifestyle interventions.”
Lowered Delta Activity in Post-COVID-19 Patients with Fatigue and Cognitive Impairment
Ortelli, P., Quercia, A., Cerasa, A., Dezi, S., Ferrazzoli, D., Sebastianelli, L., Saltuari, L. L., Versace, V., & Quartarone, A. (2023) · Biomedicines · doi:10.3390/biomedicines11082228 · Cited by 14
“uk/guidance/ng188, accessed on 30 August 2022) has recently updated the informal term for a combination of symptoms that appear or last longer than 4 weeks after the first COVID-19 infection and cannot be adequately explained by another diagnosis as post-COVID-19 syndrome (PCS) [1].”
Background
Neuroanatomical signatures associated with dispositional optimism predict COVID-19-related posttraumatic stress symptoms
Lai, H., Zhao, Y., Li, J., Gong, Q., & Wang, S. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad211 · Cited by 22
Hydroxytyrosol and Arginine as Antioxidant, Anti-Inflammatory and Immunostimulant Dietary Supplements for COVID-19 and Long COVID
de la Lastra, J. M. P., Andrés, C. M. C., Andrés, C., Plou, F. J., & Pérez‐Lebeña, E. (2023) · Foods · doi:10.3390/foods12101937 · Cited by 17
“and neurological signs and symptoms, including dyspnea, fatigue, cardiac arrhythmias, heartburn, and memory and concentration problems (sometimes known as “brain fog”) with a substantial impact on quality of life [5].”
Background
Prolonged Symptoms after COVID-19 in Japan: A Nationwide Survey of the Symptoms and Their Impact on Patients’ Quality of Life
Honda, H., Takamatsu, A., Miwa, T., Tabuchi, T., Taniguchi, K., Shibuya, K., & Tokuda, Y. (2023) · The American Journal of Medicine · doi:10.1016/j.amjmed.2023.04.040 · Cited by 15
Long COVID active case detection initiative among COVID-19 patients in Port Dickson, Malaysia: a retrospective study on the positive outcomes, the proportion of patients with long COVID and its associated factors
Wan, K. S., Sundram, E. R., Haddi, A. A. A., Dashuki, A. R., Ahad, A. M., John, R., Wahid, M. R. A., Halmie, U. I. F. U., Ibrahim, F. E., & Rahim, N. B. A. (2023) · PeerJ · doi:10.7717/peerj.14742 · Cited by 16
“Long COVID symptoms Our most common long COVID symptom of fatigue is similar to many studies (Cabrera Martimbianco et al., 2021; Crook et al., 2021;D’Cruz et al., 2021;Moy et al., 2022).”
Background
Functional neurological disorders after COVID-19 and SARS-CoV-2 vaccines: a national multicentre observational study
Alonso-Canovas, A., Kurtis, M., Gómez-Mayordomo, V., Macías-García, D., Viedma, Á. G., Rezola, E. M., Pagonabarraga, J., Orgaz, L. A., Masjuán, J., Martínez-Castrillo, J., et al. (2023) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2022-330885 · Cited by 16
Long COVID in children and adolescents: COVID-19 follow-up results in third-level pediatric hospital
Balderas, L. M. D. C. J., Fernández, A. N., Garza, S. A. D., Jerves, M. I. O., Figueroa, W. E. S., Koretzky, S. G., Márquez-González, H., Klünder-Klünder, M., Espinosa, J. G., Nieto-zermeno, J., et al. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2023.1016394 · Cited by 16
“In children, the manifestations of COVID-19 in the acute phase are considered mild compared with those in adults (5, 6); however, some children experience a severe disease that requires hospitalization, with a worse prognosis because of comorbidities (7, 8).”
Background
Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?
Leitzke, M. (2023) · Bioelectronic Medicine · doi:10.1186/s42234-023-00104-7 · Cited by 30
“This makes therapeutic approaches to long-haul COVID speculative (Crook et al. 2021; Tirelli et al. 2021) at best with rather dissatisfying effectiveness (Scordo et al.”
Background
Impact of COVID-19 vaccination in post-COVID cardiac complications
Parodi, J. B., Indavere, A., Jacob, P. B., Toledo, G., Micali, R. G., Waisman, G. D., Masson, W. M., Epstein, E. D., & Huerin, M. S. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.01.052 · Cited by 19
Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation
Dufrusine, B., Valentinuzzi, S., Bibbò, S., Damiani, V., Lanuti, P., Pieragostino, D., Boccio, P. D., D’Alessandro, E., Rabottini, A., Berghella, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010015 · Cited by 17
Complications Following Elective Major Noncardiac Surgery Among Patients With Prior SARS-CoV-2 Infection
Quinn, K. L., Huang, A., Bell, C. M., Detsky, A. S., Lapointe‐Shaw, L., Rosella, L. C., Urbach, D. R., Razak, F. A., & Verma, A. A. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.47341 · Cited by 19
Prevalence of Long-COVID Among Low-Income and Marginalized Groups: Evidence From Israel
Heller, O., Chun, Y., Shapira, S., Troen, A. M., Shlomo, Y., Acri, M. C., Marotta, P. L., Kulkarni, S., Kinnison, B., & Grinstein‐Weiss, M. (2022) · International Journal of Public Health · doi:10.3389/ijph.2022.1605086 · Cited by 19
“While the acute symptoms of COVID-19 infection typically remit after several weeks, a concerning proportion of individuals experience lingering symptoms that persist for months after infection (1, 7).”
Background
Post COVID and Apheresis – Where are we Standing?
Steenblock, C., Walther, R., Tselmin, S., Jarzebska, N., Voit-Bak, K., Toepfner, N., Siepmann, T., Passauer, J., Hugo, C., Wintermann, G., et al. (2022) · Hormone and Metabolic Research · doi:10.1055/a-1945-9694 · Cited by 16
Monocytosis in the acute phase of SARS-CoV-2 infection predicts the presence of anosognosia for cognitive deficits in the chronic phase
Nuber‐Champier, A., Voruz, P., de Alcântara, I. J., Bréville, G., Allali, G., Lalive, P. H., Assal, F., & Péron, J. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100511 · Cited by 13
“This is, nevertheless, no easy task, as the pathways associated with the neurotropism of SARS-CoV-2 are not yet well established (for reviews, see (Crook et al., 2021; Damiano et al., 2021).”
Predictors of chronic COVID-19 symptoms in a community-based cohort of adults
Silverberg, J., Zyskind, I., Naiditch, H., Zimmerman, J., Glatt, A., Pinter, A., Theel, E., Joyner, M., Hill, D. A., Lieberman, M. R., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0271310 · Cited by 16
“Previous studies showed complications of COVID-19 affecting virtually every organ system [14].”
Background
Anti-fatigue effect from Ginseng Radix et Rhizoma: a suggestive and promising treatment for long COVID
Zhou, X.-D., Zhang, K.-Y., Liu, L.-B., Zhao, Q., Huang, M., Shao, R., Wang, Y.-Y., Qu, B., & Wang, Y. (2022) · Acupuncture & Herbal Medicine · doi:10.1097/hm9.0000000000000033 · Cited by 16
“Compared with overtiredness, fatigue is a more profound state which leads to the constant weariness that impairs a person’s vitality, determination, and concentration([10]).”
Background
Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Siberry, V. G. R., & Rowe, P. (2022) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000003477 · Cited by 16
“In the adult population, female sex and asthma have been associated with increased risk of developing long COVID.(6)”
Background
Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review
Patil, M. S., Richter, E., Fanning, L., Hendrix, J., Wyns, A., Barrero-Santiago, L., Nijs, J., Godderis, L., & Polli, A. (2024) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2024.32 · Cited by 15
“10).”
Background
Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection
Soare, I.-A., Ansari, W., Nguyen, J. L., Mendes, D., Ahmed, W., Atkinson, J., Scott, A., Atwell, J. E., Longworth, L., & Becker, F. (2024) · Health and Quality of Life Outcomes · doi:10.1186/s12955-024-02230-5 · Cited by 17
“In the survey, long COVID was defined according to the National Institute for Health and Care Excellence (NICE) as symptoms which cannot be explained by an alternative diagnosis or condition and which lasted or developed 12 weeks beyond the initial COVID-19 infection [6, 11].”
BackgroundMethodInfluential
The long-term effects of the Covid-19 infection on cardiac symptoms
Vafa, R. G., Heydarzadeh, R., Rahmani, M., Tavan, A., Mansorkhani, S. K., Zamiri, B., Amiri, F., Azadian, A., Khademolhosseini, A., Montaseri, M., et al. (2023) · BMC Cardiovascular Disorders · doi:10.1186/s12872-023-03322-8 · Cited by 17
“Finally, it seems that different mechanisms and factors have roles in the presence of fatigue in the long-term [51].”
Background
“Long COVID-19” and viral “fibromyalgia-ness”: Suggesting a mechanistic role for fascial myofibroblasts (Nineveh, the shadow is in the fascia)
Plaut, S. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.952278 · Cited by 15
Lessons Learnt from COVID-19: Computational Strategies for Facing Present and Future Pandemics
Pavan, M., & Moro, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054401 · Cited by 25
Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection
Rizvi, A., Ziv, Y., Crawford, J. M., & Trindade, A. J. (2023) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2022.09.002 · Cited by 17
“Evidence is accumulating that long COVID is a multiorgan disease, involving the cardiopulmonary, neurologic, gastrointestinal (GI), nephrological, and other systems.(3,4) Substantial debate exists regarding the delineation of long COVID syndrome.”
Background
Expert guidance on the management and challenges of long-COVID syndrome: a systematic review
Ora, J., Calzetta, L., Frugoni, C., Puxeddu, E., & Rogliani, P. (2022) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2022.2161365 · Cited by 19
“Today, the epidemic seems to be in its descendant phase, when the disease is less severe and more spread; however, another more subtle and unpredictable epidemic is spreading and it is called ‘longCOVID’ [2,3].”
Background
“I Am Not the Same as I Was Before”: A Qualitative Analysis of COVID-19 Survivors
Duan, E., Garry, K., Horwitz, L. I., & Weerahandi, H. M. (2022) · International Journal of Behavioral Medicine · doi:10.1007/s12529-022-10129-y · Cited by 13
“Long COVID” results after hospitalization for SARS-CoV-2 infection
Rigoni, M., Torri, E., Nollo, G., Donne, L. D., Rizzardo, S., Lenzi, L., Falzone, A., & Cozzio, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-13077-5 · Cited by 15
Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol
Chandan, J. S., Brown, K. R., Simms-Williams, N., Camaradou, J., Bashir, N. Z., Heining, D., Aiyegbusi, O. L., Turner, G., Rivera, S. C., Hotham, R., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-057885 · Cited by 20
Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome
Block, T., & Kuo, J. C. (2022) · Clinical Pathology · doi:10.1177/2632010x221106986 · Cited by 17
“The heterogeneity of persisting symptoms contributes to the complex diagnosis of PACS, so categorizing PACS into subsets based on the predominant organ systems involved may help identify the etiology of this condition: (1) post-acute COVID cardiovascular syndrome, (2) post-acute COVID pulmonary syndrome, (3) post-acut…”
Background
Prevalence and duration of common symptoms in people with long COVID: a systematic review and meta-analysis
Luo, S., Lai, L. Y. H., Zhu, R., Gao, Y., & Zhao, Z. (2025) · Journal of Global Health · doi:10.7189/jogh.15.04282 · Cited by 16
“Crook and colleagues [ 11 ] highlighted that long COVID could involve multiple organs and affect many systems, while Sudre and colleagues [ 12 ] found it was characterised by symptoms of fatigue, headache, shortness of breath, and anos-mia, and reported a positive correlation between the likelihood…”
The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19
Li, J., Kong, X., Liu, T., Xian, M., & Wei, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25189960 · Cited by 17
“Additionally, therapies targeting ACE2 could offer promising treatment strategies for patients suffering from long COVID [117].”
Background
Differences in brain structure and cognitive performance between patients with long-COVID and those with normal recovery
Nelson, B. K., Farah, L. N., Grier, A., Su, W., Chen, J., Sossi, V., Sekhon, M. S., Stoessl, A. J., Wellington, C. L., Honer, W. G., et al. (2024) · NeuroImage · doi:10.1016/j.neuroimage.2024.120859 · Cited by 16
“…include female sex, a higher number of symptoms during acute COVID-19, hospitalization for acute COVID-19, and pre-existing psychiatric illness (Crook, et al., 2021; Townsend, et al., 2020; Whi-taker, et al., 2022; Ocsovszky, et al., 2022), suggesting a complex bio-psychosocial pathogenesis.”
Background
Long COVID Among People With Preexisting Disabilities.
Hall, J. P., Kurth, N. K., McCorkell, L., & Goddard, K. S. (2024) · American Journal of Public Health · doi:10.2105/ajph.2024.307794 · Cited by 14
An Adaptive Pacing Intervention for Adults Living With Long COVID: A Narrative Study of Patient Experiences of Using the PaceMe app
Meach, R., Carless, D., Sanal‐Hayes, N. E. M., Mclaughlin, M., Hayes, L. D., Mair, J. L., Ormerod, J. A., Hilliard, N., Ingram, J., & Sculthorpe, N. F. (2024) · Journal of Patient Experience · doi:10.1177/23743735241272158 · Cited by 14
“6 While several guidelines on long COVID have been published, the absence of a practical and effective means to guide patient rehabilitation has resulted in clinical practice adopting a symptom-based approach.”
Mechanistic and thermodynamic characterization of antiviral inhibitors targeting nucleocapsid N-terminal domain of SARS-CoV-2
Dhaka, P., Singh, A., Choudhary, S., Peddinti, R. K., Kumar, P., Sharma, G. K., & Tomar, S. (2023) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2023.109820 · Cited by 17
COVID-19 and health systems in Brazil and around the world: effects on the working conditions and health of health workers
Machado, A. V., Ferreira, W. E., Vitória, M., Júnior, H. M. M., Jardim, L. L., Menezes, M. A. C., Santos, R. P. D. O., Vargas, F. L., & Pereira, E. J. (2023) · Ciência & Saúde Coletiva · doi:10.1590/1413-812320232810.10102023 · Cited by 61
Frailty as a risk factor for post‐acute sequelae of COVID ‐19 among US veterans during the Delta and Omicron waves
Hammel, I. S., Tosi, D. M., Tang, F., Pott, H., & Ruiz, J. G. (2023) · Journal of the American Geriatrics Society · doi:10.1111/jgs.18584 · Cited by 15
“…changes may lead to heightened viral-induced multi-organ damage characterized by fibrotic changes, hypercoagulability, and endothelial injury 4,5 ; persistence of the virus in blood and other organs 3,4 ; and impaired responses to vaccination which may further compromise older persons'…”
BackgroundResultInfluential
A Learning Health System for Long Covid Care and Research in British Columbia
Naik, H., Malbeuf, M., Shao, S., Wong, A., Tran, K., Russell, J. A., Lavallee, D., Carlsten, C., Ryerson, C., & Levin, A. (2023) · NEJM Catalyst · doi:10.1056/cat.23.0120 · Cited by 14
Probable COVID-19 infection is associated with subsequent poorer mental health and greater loneliness in the UK COVID-19 Mental Health and Wellbeing study
Wilding, S., O'Connor, D. B., Ferguson, E., Cleare, S., Wetherall, K., O’Carroll, R. E., Robb, K. A., & O’Connor, R. C. (2022) · Scientific Reports · doi:10.1038/s41598-022-24240-3 · Cited by 23
“This along with the results of the present study support the idea that contracting COVID-19 is associated with both physical [14, 24] and mental health impairments.”
BackgroundResult
Temporal model for central sensitization: A hypothesis for mechanism and treatment using systemic manual therapy, a focused review
Halili, A. (2022) · MethodsX · doi:10.1016/j.mex.2022.101942 · Cited by 16
Consensus elements for observational research on COVID-19-related long-term outcomes
Admon, A. J., Wander, P. L., Iwashyna, T. J., Ioannou, G. N., Boyko, E. J., Hynes, D. M., Bowling, C. B., Bohnert, A. S. B., O’Hare, A. M., Smith, V. A., et al. (2022) · Medicine · doi:10.1097/md.0000000000031248 · Cited by 16
“[2,7,26] The exercise we describe offers a number of important insights that may be helpful in guiding future research efforts.”
The German COVID-19 Digital Contact Tracing App: A Socioeconomic Evaluation
Ellmann, S., Maryschok, M., Schöffski, O., & Emmert, M. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192114318 · Cited by 15
Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial
Voci, D., Götschi, A., Held, U., Bingisser, R. M., Colucci, G., Duerschmied, D., Fumagalli, R. M., Gerber, B., Hasse, B. K., Keller, D. I., et al. (2022) · Thrombosis Research · doi:10.1016/j.thromres.2022.10.021 · Cited by 19
Implications for long COVID : A systematic review and meta‐aggregation of experience of patients diagnosed with COVID ‐19
Zheng, X., Qian, M., Ye, X., Zhang, M., Zhan, C., Li, H., & Luo, T. (2022) · Journal of Clinical Nursing · doi:10.1111/jocn.16537 · Cited by 18
“It can decrease the possibility of returning to work (Chopra et al., 2021), increase stress disorders (Crook et al., 2021), lead to the loss of social connections (Torales et al., 2020), and decrease the quality of life (Laurie et al., 2020).”
Background
Post-COVID-19 syndrome symptoms after mild and moderate SARS-CoV-2 infection
Al-Husinat, L., Nusir, M., Al-Gharaibeh, H., Alomari, A. A., Smadi, M. M., Battaglini, D., & Pelosi, P. P. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.1017257 · Cited by 18
Exploring the lived experience of Long Covid in black and minority ethnic groups in the UK: Protocol for qualitative interviews and art-based methods
Smyth, N., Alwan, N., Band, R., Chaudhry, A., Chew-Graham, C., Gopal, D., Jackson, M., Kingstone, T., Wright, A., & Ridge, D. (2022) · PLoS ONE · doi:10.1371/journal.pone.0275166 · Cited by 14
“Symptoms can be physical, cognitive or mental, affecting multiple bodily systems [4, 5].”
Background
Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review
Morello, R., Rose, C. D., Cardinali, S., Valentini, P., & Buonsenso, D. (2022) · Children · doi:10.3390/children9101446 · Cited by 18
“Since its discovery, the SARS-CoV-2 virus has had a great impact on people’s health, including children [1].”
Background
The Impact of COVID-19 Related Social Distancing on Mental Health Outcomes: A Transdiagnostic Account
Spencer-Laitt, D., Eustis, E. H., Barlow, D. H., & Farchione, T. J. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116596 · Cited by 32
The Short- and Long-Term Clinical, Radiological and Functional Consequences of COVID-19
Gao, Y., Liang, W., Li, Y., He, J., & Guan, W. (2022) · Archivos de Bronconeumología · doi:10.1016/j.arbres.2022.03.006 · Cited by 15
Comparative Study of Early Impacts of Post-COVID-19 Pneumonia on Clinical Manifestations, Pulmonary Function, and Chest Radiographs
Niyatiwatchanchai, N., Deesomchok, A., Chaiwong, W., Duangjit, P., Pothirat, C., Liwsrisakun, C., Bumroongkit, C., Theerakittikul, T., Limsukon, A., Tajarernmuang, P., et al. (2022) · Medicina · doi:10.3390/medicina58020216 · Cited by 14
“The post-COVID-19 sequelae can affect various organs and can be explained by ongoing chronic inflammation and tissue damage [12].”
Background
Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients
Tilikete, C., Zamali, I., Meddeb, Z., Kharroubi, G., Marzouki, S., Dhaouadi, T., Hmid, A. B., Samoud, S., Galai, Y., Charfeddine, S., et al. (2024) · BMC Infectious Diseases · doi:10.1186/s12879-024-10222-5 · Cited by 13
“Furthermore, research has indicated that IL-8 is involved in the pathogenesis of chronic inflammatory lung diseases [42] and plays a pivotal role in the development of pulmonary fibrosis, a condition often associated with persistent dyspnea in PCS patients [43].”
Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study
Wang, J., Goodfellow, H., Walker, S., BLANDFORD, A. E., Pfeffer, P., Hurst, J. R., Sunkersing, D., Bradbury, K. J., Robson, C., Henley, W., et al. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-088538 · Cited by 15
Long-COVID autonomic syndrome in working age and work ability impairment
Rinaldi, L., Rigo, S., Pani, M., Bisoglio, A., Khalaf, K., Minonzio, M., Shiffer, D., Romeo, M. A., Verzeletti, P., Ciccarelli, M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-61455-y · Cited by 14
Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach
Calcaterra, V., Zanelli, S., Foppiani, A., Verduci, E., Benatti, B., Bollina, R., Bombaci, F., Brucato, A. L., Cammarata, S., Calabrò, E., et al. (2024) · Diseases · doi:10.3390/diseases12050095 · Cited by 17
Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems
Sideratou, C.-M., & Papaneophytou, C. P. (2023) · Infectious Disease Reports · doi:10.3390/idr15060072 · Cited by 23
“As aforementioned, cytokine storm, a systemic hyperinflammatory state characteristic of the acute phase of COVID-19, activates neuroglial cells and increases the risk of neurological complications post-infection [96].”
Background
Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome
Varillas-Delgado, D., Jiménez-Antona, C., Lizcano-Álvarez, Á., Cano-de-la-Cuerda, R., Molero‐Sánchez, A., & Laguarta-Val, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316717 · Cited by 13
“Patients who experience more severe disease during the acute phase appear to have a higher risk of developing persistent symptoms [39,40].”
Background
Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review
Paramythiotis, D., Karlafti, E., Didagelos, M., Fafouti, M. E., Veroplidou, K., Protopapas, A. A., Kaiafa, G. D., Netta, S., Michalopoulos, A., & Savopoulos, C. G. (2023) · Medicina · doi:10.3390/medicina59111961 · Cited by 15
“…are mainly expressed in the lung parenchyma, but they are also present in many other cell types, such as in the oral and nasal mucosa, gastrointestinal (GI) tract, pancreas, liver, kidneys, heart, spleen, brain, Medicina 2023 , 59 , 1961 2 of 14 and the endothelial cells of blood vessels [1,5].”
BackgroundInfluential
Metabolic Fingerprinting for the Diagnosis of Clinically Similar Long COVID and Fibromyalgia Using a Portable FT-MIR Spectroscopic Combined with Chemometrics
Hackshaw, K. V., Yao, S., Bao, H., Castellví, S. D. L., Aziz, R., Nuguri, S. M., Yu, L., Osuna-Diaz, M. M., Brode, W. M., Sebastian, K., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11102704 · Cited by 16
Profile of long COVID symptoms needing rehabilitation: a cross-sectional household survey of 12,925 SARS-CoV-2 cases between July and December 2021 in Bangladesh
Kabir, M. F., Yin, K. N., Jeffree, M., Ahmedy, F., Jahan, S., Islam, M. W., Jahid, I., Sivan, M., Chakrovorty, S. K., & Hossain, K. M. A. (2023) · Archives of Public Health · doi:10.1186/s13690-023-01140-0 · Cited by 13
“The management of LC is multidisciplinary as the condition impacts multiple organs in humans [6].”
Background
Job loss and mental disorders: International evidence from the early stages of COVID‐19 outbreak
Zamanzadeh, A., Banerjee, R., & Cavoli, T. (2023) · Stress and Health · doi:10.1002/smi.3287 · Cited by 12
Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension
Baalbaki, N., Blankestijn, J. M., Abdel‐Aziz, M. I., Backer, J. D., Bazdar, S., Beekers, I., Beijers, R. J. H. C. G., van den Bergh, J. P., Bloemsma, L. D., Bogaard, H. J., et al. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13071060 · Cited by 21
The controversial effect of smoking and nicotine in SARS-CoV-2 infection
Salehi, Z., Gh, B. F. N. M., Nourian, Y. H., Jamalkandi, S. A., & Ghanei, M. (2023) · Allergy Asthma and Clinical Immunology · doi:10.1186/s13223-023-00797-0 · Cited by 18
“Postacute COVID-19 syndrome, like COVID-19, can impact various systems and organs, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems [180].”
Background
Strategies for the Management of Spike Protein-Related Pathology
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Faghy, M. A., Whitsel, L. P., Arena, R. A., Smith, A., & Ashton, R. E. M. (2023) · Journal of Public Health Policy · doi:10.1057/s41271-023-00409-6 · Cited by 14
“Those with unhealthy lifestyle characteristics run greater risks of severe outcomes during acute infection [32] and increased risks of developing long-term sequelae [33].”
Background
A Review of Clinical Laboratory Education, Training and Progression: Historical Challenges, the Impact of COVID-19 and Future Considerations
Pearse, C., & Scott, S. (2023) · British Journal of Biomedical Science · doi:10.3389/bjbs.2023.11266 · Cited by 27
The Thai version of the COVID-19 Yorkshire Rehabilitation Scale: a valid instrument for the psychometric assessment of the community members in Bangkok, Thailand
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Post‐COVID‐19‐associated multiorgan complications or “long COVID” with literature review and management strategy discussion: A meta‐analysis
Iqbal, P., Ata, F., Chaudhry, H., Muthanna, B., Younas, H. W., Munamm, S. A. U., Sharma, R. K., Fadah, K., Elazzazy, S., Hamad, A. A., et al. (2023) · Health Science Reports · doi:10.1002/hsr2.1211 · Cited by 15
“Our study has consolidated the symptoms according to the specific organ/system involved, as mentioned in Table 1, cementing the evidence of long COVID.”
BackgroundMethodInfluential
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Wang, S., Farland, L. V., Gaskins, A. J., Mortazavi, J., Wang, Y., Tamimi, R. M., Rich-Edwards, J. W., Zhang, D., Terry, K. L., Chavarro, J. E., et al. (2023) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2023.03.030 · Cited by 18
“In addition, organs and tissues expressing angiotensinconverting enzyme 2 (ACE2) (the receptor for SARS-CoV-2), such as heart, lung, tongue, and blood vessels, are susceptible to direct damage by the virus itself and inflammation.(3) Because ACE2 is expressed in endometrial tissue, ectopic endometrium may predispose w…”
Prospects and possibilities for the treatment of patients with long COVID-19 syndrome
Tanashyan, M. М., Раскуражев, А. А., Игоревна, К. П., Bely, P. A., & Zaslavskaya, K. Y. (2022) · Terapevticheskii arkhiv · doi:10.26442/00403660.2022.11.201981 · Cited by 14
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“Chronic systemic inflammation is frequently observed long after the clearance of acute COVID-19 infection [17].”
Patients’ Health Experiences of Post COVID-19 Condition—A Qualitative Study
Almgren, J., Löfström, E., Malmborg, J. S., Nygren, J., Undén, J., & Larsson, I. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192113980 · Cited by 13
“[34] highlight that fatigue is a common symptom of long-term COVID-19 and the symptoms may overlap with chronic fatigue syndrome.”
Background

Authors: Crook, H., Raza, S., Nowell, J., Young, M., & Edison, P.
Affiliations: Imperial College London (GB)
Corresponding author: Edison, Paul
ORCID: Edison, Paul
Venue: BMJ
Publisher: BMJ
Published: 2021-07-26
Volume: 374
Pages: n1648
ISSN: 1756-1833 (ISSN-L)
DOI: 10.1136/bmj.n1648
OpenAlex: W3186314395
Cited by: 1,655
References: 0
Citations by year: 2026: 85 · 2025: 205 · 2024: 329 · 2023: 508 · 2022: 466 · 2021: 60
FWCI: 43.57
Type: journal article
Language: en
Update notices: correction (2021-08-03)
Open access: closed
Licence: bmj.com/coronavirus/usage (tdm)
Locations: BMJ (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords: long COVID, SARS-CoV-2, persistent symptoms, fatigue, dyspnea, cardiac anomalies, cognitive impairment, sleep disorders, post-traumatic stress disorder, myalgia, risk factors, treatment options
MeSH terms: Global Burden of Disease, COVID-19, Post-Acute COVID-19 Syndrome, Clinical Trials as Topic, Combined Modality Therapy, Humans, Risk Factors, Severity of Illness Index, Incidence, Practice Guidelines as Topic, Drug Repositioning

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Long covid—mechanisms, risk factors, and management

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